Transplantation of basic fibroblast growth factor-pretreated adipose tissue-derived stromal cells enhances regression of liver fibrosis in mice

Kamada, Y.; Yoshida, Yasuhiko; Saji, Yukiko; Fukushima, Juichi; Tamura, Shinji; Kiso, Shinichi; Hayashi, Norio

doi:10.1152/ajpgi.90463.2008

Cited by 34 publications

(34 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The livers of the CCl 4 +AFSCs group had a normal histological appearance 10 d after the injury, whereas inflammatory infiltration and small foci of necrosis were evident in the CCl 4 group at that stage, even though the groups did not differ in terms of biochemical markers of liver function. This result is consistent with the results of studies on cell-based therapy for liver disease (Ochenashko et al 2006;Kamada et al 2009;Yan et al 2009). In these studies, numbers of grafted human cells were small in comparison with those of the host hepatocytes.…”

Section: Discussionsupporting

confidence: 91%

Human amniotic fluid-derived stem cells can differentiate into hepatocyte-like cells in vitro and in vivo

Liu

Liu²,

Li³

et al. 2011

In Vitro Cell.Dev.Biol.-Animal

View full text Add to dashboard Cite

Although human amniotic fluid is an attractive source of multipotent stem cells, the potential of amniotic fluid stem cells (AFSCs) to differentiate into hepatic cells has not been extensively evaluated. In this study, we examined whether human AFSCs can differentiate into a hepatic cell lineage in vitro and in vivo. After being treated with cytokines (fibroblast growth factor 4, basic fibroblast growth factor, hepatocyte growth factor, and oncostatin), AFSCs developed a morphology similar to that of hepatocytes. RT-PCR and immunofluorescence analysis showed that the treated AFSCs expressed the hepatocyte-specific markers albumin, cytokeratin 18, and alpha-fetoprotein. The differentiated cells also developed hepatocyte-specific functions, i.e., they secreted albumin, absorbed indocyanine green, and stored glycogen. When transplanted into CCl(4)-injured immunodeficient mice, undifferentiated AFSCs were integrated into the liver tissue, and they expressed markers characteristic of mature human hepatocytes. Although integration of AFSCs into the liver was limited (0.1-0.3% of hepatocytes), histological analysis showed that the recipient mice recovered more rapidly from CCl(4) injury than CCl(4)-injured mice that did not receive AFSCs. AFSCs can differentiate into hepatocyte-like cells in vitro and in vivo and can represent an easily accessible source of progenitor cells for hepatocyte regeneration and liver cell transplantation.

show abstract

Section: Discussionsupporting

confidence: 91%

Human amniotic fluid-derived stem cells can differentiate into hepatocyte-like cells in vitro and in vivo

Liu

Liu²,

Li³

et al. 2011

In Vitro Cell.Dev.Biol.-Animal

View full text Add to dashboard Cite

show abstract

“…2g-k). This is entirely consistent with the results of the morphological analysis by Kamada et al (2009). Overall, cell morphological changes in the liver extract-induction group were sooner than that in the chemical group.…”

Section: Resultssupporting

confidence: 90%

A comparison of the chemical and liver extract-induced hepatic differentiation of adipose derived stem cells

Nhung

Nam

Nguyen

et al. 2015

In Vitro Cell.Dev.Biol.-Animal

View full text Add to dashboard Cite

Adipose-derived stem cells (ADSCs) have been put forward as promising therapeutics for end-stage liver disease (ESLD). In the present study, we compared the effects of defined chemicals and liver extract on the hepatic differentiation of ADSCs. ADSCs were isolated according to the method described in our previously published study. Subsequently, the differentiation of ADSCs was induced separately by chemicals (including hepatic growth factor (HGF), fibroblast growth factor (FGF), and oncostatin M (OSM)) and liver extract (30 μg/ml) in a total period of 21 d. The efficiency of hepatic differentiation was evaluated by changes in the cell morphology, gene expression, and cellular function. The results showed that the liver extract promoted the hepatic differentiation of ADSCs to a significantly greater extent than the chemicals. In the group of ADSCs treated with liver extract, changes in the cell morphology began sooner, and the expression of alpha-FP and albumin genes was higher than that in the chemically treated group. The ADSCs in both the groups stained positive for anti-alpha trypsin (AAT) and albumin markers. The cells also exhibited glycogen storage capacity. Therefore, we concluded that the liver extract could efficiently induce the differentiation of ADSCs into hepatocyte-like cells. This study reveals the potential of mesenchymal stem cell differentiation in the liver extract, which supports further preclinical and clinical research on the application of ADSCs in ESLD treatment.

show abstract

“…In one study, fibroblast growth factor-treated stromal cells derived from adipose tissue had the potential to reverse fibrotic liver injury. 34 Although this is an exciting finding, the biology underlying this phenomenon is not completely understood. One possible mechanistic link between adipose tissue and stellate cells is their exclusive ability to store retinoids, which appear to play a pivotal role in maintaining stellate cell quiescence and modulation of fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Adiponectin Regulation of Stellate Cell Activation via PPARγ-Dependent and -Independent Mechanisms

Shafiei

Shetty

Scherer

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

In this study, we elucidated the mechanism by which adiponectin modulates hepatic stellate cell activation and fibrogenesis. Adiponectin-overexpressing transgenic mice receiving thioacetamide were resistant to fibrosis, compared with controls. In contrast, adiponectin-null animals developed severe fibrosis. Expression of collagen ␣1(I) and ␣-smooth muscle actin (␣-SMA) mRNAs were significantly lower in adiponectin-overexpressing mice, compared with controls. In wild-type stellate cells exposed to a lentivirus encoding adiponectin, expression of peroxisome proliferator-activated receptor-␥ (PPAR␥), SREBP1c, and CEBP␣ mRNAs was significantly increased (3.2-, 4.1-, and 2.2-fold, respectively; n ‫؍‬ 3; P < 0.05, adiponectin virus versus control), consistent with possible activation of an adipogenic transcriptional program. Troglitazone, a PPAR␥ agonist, strongly suppressed upregulation of collagen ␣1(I) and ␣-SMA mRNA in stellate cells isolated from wild-type mice; however, stellate cells from adiponectin-null animals failed to respond to troglitazone. Furthermore, in isolated stellate cells in which PPAR␥ was depleted using an adenovirus-Cre-recombinase system and in which adiponectin was also overexpressed, collagen ␣1(I) and ␣-SMA were significantly inhibited. We conclude that the PPAR␥ effect on stellate cell activation and the fibrogenic cascade appears to be adiponectin-dependent; however, the inhibitory effect of adiponectin on stellate cell activation was not dependent on PPAR␥, suggesting the presence of PPAR␥-dependent as well as independent pathways in stellate cells.

show abstract

Transplantation of basic fibroblast growth factor-pretreated adipose tissue-derived stromal cells enhances regression of liver fibrosis in mice

Cited by 34 publications

References 36 publications

Human amniotic fluid-derived stem cells can differentiate into hepatocyte-like cells in vitro and in vivo

Human amniotic fluid-derived stem cells can differentiate into hepatocyte-like cells in vitro and in vivo

A comparison of the chemical and liver extract-induced hepatic differentiation of adipose derived stem cells

Adiponectin Regulation of Stellate Cell Activation via PPARγ-Dependent and -Independent Mechanisms

Contact Info

Product

Resources

About